Journal
TOXICOLOGY
Volume 243, Issue 3, Pages 294-302Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2007.10.018
Keywords
dimethyl 2,2-dichlorovinyl phosphate (DDVP, dichlorvos); flow cytometry; granzyme B; granzyme 3/K; immunofluorescence microscopy
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Natural killer (NK), lymphokine-activated killer (LAK), and cytotoxic T lymphocyte (CTL) cells kill target cells by the directed release of cytolytic granules that contain perforin, granzymes, and granulysin. We have found previously that dimethyl 2,2-dichlorovinyl phosphate (DDVP, dichlorvos), an organophosphorus pesticide, significantly decreased the expression of perforin, granzyme A (GrA), and granulysin and inhibited NK, LAK, and CTL activities. To further explore the mechanism of organophosphorus pesticide-induced inhibition of cell-mediated cytolysis, we examined whether organophosphorus pesticides affect the expression of GrB and Gr3/K in NK cells. We used an interleukin-2 (IL-2) independent human NK cell line, NK-92CI. We confirmed that NK-92CI cells express intracellular GrB and Gr3/K by flow cytometry, that NK-92CI cells are highly cytotoxic to K562 cells with a chromium release assay, and that DDVP significantly inhibited cytolytic activity of NK-92CI cells in a dose- and time-dependent manner. We found that DDVP significantly decreased the expression of GrB and Gr3/K in NK-92CI cells in a dose- and time-dependent manner by flow cytometry. Immunocytochemical results showed that DDVP significantly decreases the level of GrB positive granules in NK-92CI cells, which may be due to degranulation. Taken together, DDVP significantly inhibits NK activity and reduces the intracellular GrB and Gr3/K levels in NK cells. (C) 2007 Elsevier Ireland Ltd. All rights reserved.
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